IN-VITRO ASSESSMENT OF THE EFFECT OF HALOGENATED HYDROCARBONS - CHLOROFORM, DICHLOROMETHANE, AND DIBROMOETHANE ON EMBRYONIC-DEVELOPMENT OF THE RAT

Halogenated hydrocarbons are widely used in industry, the laboratory, and in the home. In the present study three of these solvents-chlorofo rm, dichloromethane, and dibromoethane-were examined for embryotoxic/t eratogenic potential using rat embryo culture. The results showed that each of the solvents had a concentration-dependent embryotoxic effect on the developing rat embryo in vitro. The effect and no-effect conce ntrations (expressed in mu moles/ml culture medium), respectively, for each of the halogenated hydrocarbons tested were: dibromoethane-0.33, <0.18; chloroform-2.06, 1.05; dichloromethane-6.54, 3.46. The levels of chloroform and dichloromethane found to be embryotoxic in the pre s ent study were compared to reported blood levels attained following co ntrolled human exposure. In the industrial situation, if the current e xposure levels are adhered to, chloroform and dichloromethane appear t o have little potential for reproductive toxicity in the human. Fatal or near fatal solvent levels would be required in the mother for the e mbryotoxic level to be reached. For dibromoethane, there are no report s following controlled human exposure presumably due to its carcinogen icity. In an attempt to elucidate the mechanism of embryotoxicity, his tological studies were performed after exposure of rat embryos to an e mbryotoxic level of each of the halogenated hydrocarbons studied, for increasing time periods up to the standard 40-hour culture. Marked cel l death in the neuroepithelium of the developing neural tube was a pro minent feature in all embryos exposed to an embryotoxic level of these solvents for periods of 16 hours or longer. (C) 1998 Wiley-Liss, Inc.